Currently, there are hundreds of biotechnology medicines in the development pipelines of pharmaceutical and biotechnology companies, and the numbers are predicted to increase in time. To produce such biotechnological products, large numbers of prokaryotic and eukaryotic cells are grown in fermentation systems. Prokaryotic cells, for example, bacterial cells, are physically more resilient than eukaryotic cells. Eukaryotic cells, such as mammalian cells, are more fragile and are more affected by steps in the culturing process such as centrifugation, pelleting or re-suspension which are necessary manipulations of the cells for biomanufacturing purposes.
Generally, cells are grown in large stainless-steel fermentation vats under strictly maintained and regulated conditions. The cells may be the product itself, or the cells may produce a product of interest. With either goal, the production of cellular based products is a complicated process. The cells are grown in carefully controlled culture conditions which include a balance of temperature, oxygen, acidity, and removal of waste products or an excreted product of interest. The growth and activity of the cells can be interfered with by even slightly altering the culture conditions, and can be highly inhibited by actions such as removal of media, isolation of the cells by spinning out the cells and packing them in a pellet formed by centrifugation, and resuspension of a packed pellet to reintroduce the cells into the culture conditions.
Many known cell culture methods require significant investment in capital and labor. Cell culture facilities cost millions of dollars to build and take several years. There are a limited number of existing facilities that can be used to produce the products that are currently proposed. Cell culture is currently used for production of proteins such as human insulin, vaccine proteins, enzymes for food processing, biodegradable plastics, and laundry detergent enzymes. Such products include, but are not limited to, therapeutic molecules, vaccines, and antibodies that function as diagnostic tools, therapeutic compounds, in protein-chips or biosensors.
A growing concern in biomanufacturing is recognition of the extent of materials used for production of cellular products, or how green is the technology. This concern looks at the type and amount of resources required to make therapeutic proteins and other cell culture products, and the wastes generated by mammalian cell culture and microbial fermentation processes. Manufacturing such products is relatively environmentally friendly compared with the production of small-molecule drugs and commodity petroleum-derived chemicals. However, the processes of cell culture use a lot of water, for example, in batch reactors that hold thousands of liters of culture or fermentation broth. Additionally, even more water, along with consumable processing aids, such as tubing, filters and chromatography processes, are used for downstream purification. Calculations have shown that for biologics, a current large-scale cell culture process to make a kilogram of monoclonal antibody requires more than 7,600 kg of material, divided as 7,000 kg of water, 600 kg of inorganic salts and buffers, which end up in the aqueous waste at the end of the process, 8 kg of organic solvents and 4 kg of consumables. For microbial fermentation, 15,500 kg of material is needed for 1 kg of product, with 15,000 kg being water. Using disposable equipment may add to the waste stream, whereas using reusable materials adds to the water usage.
What is needed are methods and systems that can be used in biomanufacturing systems and other types of processes that can be used with particles. The particles can be living or inert, including biomaterials and all types of cells, hardy cells and cells that require gentle treatment. What is also needed are methods and systems that do not disrupt cellular growth and activity processes during the biomanufacturing processes, and may aid in the growth and production of cells. Additionally, it would be beneficial for methods and systems to provide green technology advances to the biomanufacturing process. Methods and systems for the transfer and manipulation of particles in efficient methods are also needed.